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Identifying Citrullination Sites by Mass Spectrometry

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Protein Deimination in Human Health and Disease

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Abstract

The citrullination of arginine is one of the smallest posttranslational modifications made to proteins, by mass. Mass spectrometric methods of analysis offer the potential to not only identify sites of protein citrullination but in some instances to quantify their occurrence in diseased tissue, relative to healthy tissues. This is an emerging, if challenging, area where method and instrument selections can influence not only data quality but also throughput. Citrullination, or deimination of arginine, results in the addition of only 0.9848 Da to a peptide. Recent improvements in the accuracy and resolution of mass spectrometers, as well as the advancement of protein chemistry technology that selectively targets citrulline moieties, has allowed greater success in identifying citrullinated arginine within proteins and peptides. This chapter provides an overview of recent, successful strategies used to identify citrullination sites using modern proteomic methods that involve mass spectrometric analysis. Applications to the study of multiple sclerosis and arthritis are highlighted.

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Acknowledgments

Thanks to Amy Harms, Ph.D. (Leiden University) and Martha Vestling, Ph.D. (University of Wisconsin-Madison) for critical review of this article. The authors are grateful for funding support from NIH/NINDS grant NS046593 to H.L. for the continued support of a NINDS NeuroProteomics Core Facility at Rutgers University-New Jersey Medical School.

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Authors and Affiliations

  1. The University of Wisconsin-Stout, Menomonie, WI, USA

    Jennifer E. Grant

  2. Rutgers University-New Jersey Medical School, Newark, NJ, USA

    Hong Li

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  1. Jennifer E. Grant
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  2. Hong Li
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Correspondence to Jennifer E. Grant .

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Editors and Affiliations

  1. Department of Neurology, University of Alabama at Birmingham and The Birmingham Veterans Administration Medical Center, Birmingham, Alabama, USA

    Anthony P. Nicholas

  2. Bascom Palmer Eye Institute, University of Miami, MIAMI, Florida, USA

    Sanjoy K. Bhattacharya

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Grant, J.E., Li, H. (2014). Identifying Citrullination Sites by Mass Spectrometry. In: Nicholas, A., Bhattacharya, S. (eds) Protein Deimination in Human Health and Disease. Springer, New York, NY. https://doi.org/10.1007/978-1-4614-8317-5_19

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